Abstract |
Following infection with the trematode helminth Schistosoma mansoni, CBA mice develop severe parasite egg-induced hepatic granulomatous inflammation as well as prominent CD4(+) T helper 17 (Th17) cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. By comparison, C57BL/6 mice develop mild hepatic immunopathology, egg stimulation of DCs does not result in IL-1β and IL-23 production, and Th17 cells fail to develop. To investigate the reasons for strain-specific differences in antigen presenting cell (APC) reactivity to eggs, we performed a comparative gene profiling analysis of normal bone marrow-derived DCs (BMDCs) and found that CBA DCs display markedly elevated expression of C-type lectin receptors (CLRs). In particular, expression of CD209a, a murine homologue of human DC-specific ICAM-3-grabbing non- integrin (DC-SIGN, CD209), was strikingly higher in CBA than BL/6 DCs. High CD209a surface expression was observed in various CBA splenic and granuloma APC subpopulations; however, only DCs, and not macrophages, B cells or neutrophils, were able to induce Th17 cell differentiation in response to schistosome eggs. Lentiviral gene silencing in CBA DCs, and over-expression in BL/6 DCs, demonstrated CD209a to be critical for egg-induced DC IL-1β and IL-23 production necessary for Th17 cell differentiation and expansion. These findings reveal a novel innate parasite-sensing mechanism promoting CD4(+) Th17 cells that mediate severe immunopathology in schistosomiasis.
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Authors | Holly E Ponichtera, Miguel J Stadecker |
Journal | Experimental parasitology
(Exp Parasitol)
Vol. 158
Pg. 42-7
(Nov 2015)
ISSN: 1090-2449 [Electronic] United States |
PMID | 25913088
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Cell Adhesion Molecules
- DC-specific ICAM-3 grabbing nonintegrin
- IL1B protein, mouse
- Interleukin-1beta
- Interleukin-23
- Lectins, C-Type
- Receptors, Cell Surface
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Topics |
- Adaptive Immunity
- Animals
- Cell Adhesion Molecules
(metabolism)
- Dendritic Cells
(immunology)
- Disease Models, Animal
- Granuloma
(immunology, pathology)
- Immunity, Innate
- Interleukin-1beta
(metabolism)
- Interleukin-23
(metabolism)
- Lectins, C-Type
(metabolism)
- Mice
- Mice, Inbred CBA
- Receptors, Cell Surface
(metabolism)
- Schistosomiasis mansoni
(immunology, pathology)
- Signal Transduction
- Spleen
(cytology, immunology)
- Th17 Cells
(immunology)
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